Expression Of Tumor Suppressor Gene PTEN/PIP3 In Hepatolithiasis Associated Cholangiocarcinoma And Their Correlations

Objective The aim of this study was to learn the clinical characteristics of intra-hepatic hepatolithiasis associated cholangiocarcinoma(IHHCC) and explore expression of tumor suppressor gene PTEN/PIP3 in HL, IHHCC and their correlations.Methods and Data Collected clinical data of 25 patients with IHHCC(<5 year had 2 patients,5-10 year had 9 patients and>10 year had 14 patients) and 45 patients who had different previous history of intrahepatic bile duct lithiasis(<5 year group had 25 patients,5-10 year and>10 year each group had 10 patients) in NO 1 hospital affiliated An hui medical university from October 2006 to January 2015.All patients received surgical treatment and tissues were confirmed by biopsy, Detection of PTEN,PIP3 expression in all tissue was done by immunohistochemical examination. Clinical data includes age, sex, symptoms,previous history of bile duct surgery, imageological diagnosis(Ultrasonography, Computed tomography, MRI/MRCP, PET-CT),and clinical characteristics of HL(location, time between diagnosis and treatment), laboratory tests(content of TBIL, tumor markers),intraoperative frozen, histological differentiation, lymphnode involvement, presence of metastasis, postoperative complications and follow up 1,3,5 year survival information. Spss20.0 analyzes the results.Results 10 cases of 25 IHHCC patients were male, and remain 15 cases were female; The average age of 56±11(35 ~ 74) years, high differentiation in 5 cases, and low differentiation in 20 cases.8 cases of hilar lymph node metastasis.In HL group it contains male 22 cases, 23 cases of female; The average age of 55±13(33 ~ 77) years old. Compare with the clinical data of HL and IHHCC:The age, gender, history of biliary tract surgery, location of the bile ductstone and preoperative TBIL have no difference(P>0.05), yet,compared with the history of hepatolithiasis and concentration of serum CA199,we found IHHCC patients who had long years of history of cholangiolithiasis than HL,the same as high concentration of serum CA199.But in patients hospitalized time and operation time and postoperative complications in two groups, there are no obvious difference(P > 0.05).25 cases of IHHCC patients with clinic correct diagnosis rates of US, CT, and MRI/MRCP were 52%(13/25),64%(16/25),32%(8/25)(P>0.05),which had no difference on the diagnosis rate of IHHCC. The surgical procedure consisted hepatectomy with bile duct exploration in 20 patients(80%), 8 patients clavine rating class I- II, all cured.1 patient clavine rating class VI,dead in 1 month after hepatectomy.Overall cumulative survival rates at 1,3,and 5 years were 40%,12%,4% respectively.42 patients of HL who had surgical procedure consisted hepatectomy with bile duct exploration, 3 cases of HL patients with hepatic lobe/resection + original biliary intestinal anastomotic demolish rebuild, 12 patients with postoperative clavine class I- II, no perioperative death. 2Result:Positive PTEN expression rate in IHHCC was 32%(8/25), it significantly less than 84% of the 45 patients with HL(38/45)(P<0.05). on the contrary, positive PIP3 expression rate in IHHCC was 68%(17/25),it significantly higher than 20% of patients with HL(9/45)(P<0.05).we found positive expressi on PTEN/PIP3 correlated with concentration of CA199, the degree of tumor differentiation, tumor size(P < 0.05), while with the patient’s gender, age, serum CEA concentration, TBIL, location distribution of stones, vessel carcinoma embolus and presence of lymph node metastasis has no statistical significance. Positive PTEN expression in IHHCC patients with the 6, 12, 36 months survival was 100%, 87.5%, 25%, negative expression of PTEN patients with the 6, 12, 36 months survival time was 35%, 35% and 0(P < 0.05),the prognosis of patients with high postive expression of PTEN signal was favourable prognosis.On the contrary positive PIP3 expression in patients and negative expression in patients with the 6, 12, 36 months survival time were respectively 39%, 18%, 0 VS 39%, 100%,25%(P < 0.05), The prognosis of patients with low expression of PIP3 was higher than the high PIP3 expression in IHHCC patients.Conclusion:(1)IHHCC patients also had high rates of PTEN mutation, and high expression of PTEN/PIP3 in patients was significantly higher/lower than that of patients with lower expression on their survival time.Negative correlation between them in expression.(2)IHHCC clinical features is similarity HL clinical features, so we should be alert biliary carcinogenesis, high level tumor marker CA199 may certain help diagnose IHHCC.